Aj. Stevens et al., EXPERIMENTAL-DETERMINATION OF A DRUG TARGETING INDEX FOR S(+)IBUPROFEN USING THE RAT AIR POUCH MODEL OF INFLAMMATION, Journal of drug targeting., 2(4), 1994, pp. 333-339
We have used the rat air pouch model of inflammation and S(+)ibuprofen
as an experimental model system to enable the quantitative assessment
of the pharmacokinetic determinants of site specific drug delivery. S
(+)ibuprofen (50 & 1 mg/kg) was administered directly into six day old
air pouches immediately following the injection of the irritant carra
geenan. Serial exudate and plasma samples were collected and analysed
for ibuprofen by HPLC. The procedure was repeated following administra
tion of S(+)ibuprofen (20 & 5 mg/kg) intravenously. The parameters des
cribing events in the air pouch and plasma indicated linear kinetics o
ver the doses employed. The dose normalised AUCs were then used to for
mulate a quantitative measure of benefit for S(+)ibuprofen delivered d
irectly to the air pouch. A Drug Targeting Index (DTI) was calculated
from the ratio of AUC in the air pouch and plasma following direct int
rapouch administration divided by the same ratio following intravenous
administration and gave a value of 130. This pharmacokinetic measure
of benefit represents the maximum advantage afforded by the site speci
fic delivery of S(+)ibuprofen as the whole of the administered dose is
delivered directly to the site of action.